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Prostate Specific Antigen (prostate + specific_antigen)
Kinds of Prostate Specific Antigen Terms modified by Prostate Specific Antigen Selected AbstractsAmperometric Immunosensor for Prostate Specific Antigen Based on Co-adsorption of Labeled Antibody and Mediator in Nano-Au Modified Chitosan MembraneCHINESE JOURNAL OF CHEMISTRY, Issue 3 2008Jie-Hua LIN Abstract A quasi-reagentless amperometric immunosensor for prostate specific antigen (PSA) has been developed based on co-adsorption of horseradish peroxidase (HRP) labeled PSA antibody (anti-PSA) and tetramethyl benzidine (TMB) in nano-Au modified chitosan membrane (Au-chitosan). The immobilized TMB was used as an electron transfer mediator, which displayed a surface-controlled process at scan rates less than 45 mV/s, and a diffusion-controlled process at scan rates higher than 45 mV/s. The immunosensor with the co-immobilized anti-PSA and TMB was incubated with sample PSA antigen, and the formed immunoconjugate in the immunosensor was detected by a TMB-H2O2 -HRP electrochemical system. Under the optimal experimental conditions, PSA could be determined in the linear range from 5.0 to 30 ng·mL,1 with a detection limit of 1.0 ng·mL,1. The prepared PSA immunosensor is not only economic due to the low-cost ITO electrode obtained from industrial mass production, but also capable of batch fabrication with acceptable detection and storage stability. [source] Prostate specific antigen (PSA)-based screeningINTERNATIONAL JOURNAL OF UROLOGY, Issue 9 2008Hiroyoshi Suzuki md Deputy Editor First page of article [source] Activation of innate immunity by prostate specific antigen (PSA),THE PROSTATE, Issue 15 2006James A. Kodak Abstract BACKGROUND Prostate specific antigen (PSA) is a serine protease secreted by the prostatic epithelium. The only known function of the protein is to cleave seminogelin. We wished to determine if PSA activated peripheral blood mononuclear cells (PBMC). METHODS PBMC and selected sub-populations were cultured with purified PSA. Secretion of IFN, was measured by cytokine capture flow cytometry and enzyme-linked immunosorbent assay. RESULTS We observed secretion of IFN, and a proliferative response in PBMC cultured with PSA. We found that NK cells were the source of the IFN, but NK cells were not directly stimulated by PSA. Rather, a soluble factor secreted primarily by CD14 monocytes in response to PSA stimulated NK cells to secrete IFN,. DISCUSSION PSA induces a pro-inflammatory response that results in the secretion of INF, by NK cells. The presence of large amounts of PSA could contribute to the common finding of inflammatory infiltrates in the prostate. Prostate 66: 1592,1599, 2006. Published 2006 Wiley-Liss, Inc. [source] Fast and novel purification method to obtain the prostate specific antigen (PSA) from human seminal plasmaTHE PROSTATE, Issue 10 2006Boris Acevedo Abstract Background Prostate specific antigen (PSA) is a relevant antigen in diagnosis; follow-up, and therapeutic approaches for fighting the prostate cancer. Several methods have been published previously to obtain a high purity preparation of PSA. In general, these methods are expensive, time-consuming, laborious, and in some cases produce low yields. Methods Based on a panel of 7 anti-PSA Mab's we carried on binding and elution experiments of PSA antigen in 96-well plates. The selected Mab were immobilized in a Sepharose CL-4B activated matrix with the purpose of purify PSA from human seminal fluid. In order to optimize the purification procedure, we test several washing and elution conditions (chaotropic agents, high ionic strength solution, and extreme pH). Results We selected a high ionic strength solution (2 M MgCl2) as elution condition, and a previous washing step with a mix of two ionic solutions (2.5 M NaCl pH 8/1 M MgCl2 pH 5.5) in order to purify PSA. Using such conditions we obtained a PSA preparation with 90% of purity and 50% of recovery. Conclusion In this article, we report a simple, quickly, and non-expensive procedure to obtain free-PSA from human seminal plasma at high purity levels. Prostate 66: 1029,1036, 2006. © 2006 Wiley-Liss, Inc. [source] Expression of BAG-1 protein correlates with aggressive behavior of prostate cancers,,THE PROSTATE, Issue 8 2006Maryla Krajewska Abstract Background Differences in tumor behavior, ranging from indolent to aggressive, create a need for novel prognostic biomarkers. BAG-1 is a co-chaperone that regulates the activity of Hsp70, Bcl-2, Raf-1, growth factor, and steroid receptors (e.g., the Androgen Receptor). Methods Using immunohistochemical method, we explored BAG-1 expression in prostate cancers and its association with clinicopathological parameters. Results BAG-1 immunostaining was elevated in prostate cancer compared to normal prostatic epithelium. Higher nuclear BAG-1 in hormone-refractory (n,=,34) compared to localized untreated tumors (n,=,58) (P,<,0.0001) suggested that upregulation of the nuclear isoform may contribute to disease progression. In 64 early-stage patients (T2N0M0) treated with external-beam irradiation, cytosolic BAG-1 correlated with higher pretreatment levels of serum Prostate specific antigen (P,=,0.04) and shorter time to disease progression (P,=,0.00004). Conclusions Increased cytosolic and nuclear BAG-1 expression may denote more aggressive variants of prostate cancer. Prostate © 2006 Wiley-Liss, Inc. [source] A UK-based investigation of inter- and intra-observer reproducibility of Gleason grading of prostatic biopsiesHISTOPATHOLOGY, Issue 6 2006J Melia Aims:, The frequency of prostatic core biopsies to detect cancer has been increasing with more widespread prostate specific antigen (PSA) testing. Gleason score has important implications for patient management but morphological reproducibility data for British practice are limited. Using literature-based criteria nine uropathologists took part in a reproducibility study. Methods:, Each of the nine participants submitted slides from consecutive cases of biopsy-diagnosed cancer assigned to the Gleason score groups 2,4, 5,6, 7 and 8,10 in the original report. A random selection of slides was taken within each group and examined by all pathologists, who were blind to the original score. Over six circulations, new slides were mixed with previously read slides, resulting in a total of 47 of 81 slides being read more than once. Results:, For the first readings of the 81 slides, the agreement with the consensus score was 78% and overall interobserver agreement was , 0.54 for Gleason score groups 2,4, 5,6, 7, 8,10. Kappa values for each category were 0.33, 0.56, 0.44 and 0.68, respectively. For the 47 slides read more than once, intra-observer agreement was 77%, , 0.66. The study identified problems in core biopsy interpretation of Gleason score at levels 2,4 and 7. Patterns illustrated by Gleason as 2 tended to be categorized as 3 because of the variable acinar size and unassessable lesional margin. In slides with consensus Gleason score 7, 13% of readings were scored 6 and in slides with consensus 6, 18% of readings were scored 7. Conclusions:, Recommendations include the need to increase objectivity of the Gleason criteria but limits of descriptive morphology may have to be accepted. [source] Soluble N-cadherin in human biological fluidsINTERNATIONAL JOURNAL OF CANCER, Issue 12 2006Lara Derycke Abstract Classical cadherins such as E-, P- and N-cadherin are transmembrane proteins that mediate cell,cell adhesion, and are important in embryogenesis, maintenance of tissue integrity and cancer. Proteolytic shedding of the extracellular domain results in the generation of soluble E-, P- or N-cadherin ectodomains. Circulating soluble E- and P-cadherin have been described in the serum, and elevated levels were detected in cancer patients when compared with healthy persons. Here we report the presence of soluble N-cadherin, a 90-kD protein fragment, in the serum of both healthy persons and cancer patients, using a direct ELISA and immunoprecipitation. A correlation was found between prostate specific antigen and soluble N-cadherin, and significantly elevated levels were detected in prostate cancer follow-up patients. The N-cadherin protein is neo-expressed by carcinomas of the prostate, and is responsible for epithelial to fibroblastic transition. This is reflected by the higher concentrations of soluble N-cadherin in prostate cancer patients than in healthy persons. © 2006 Wiley-Liss, Inc. [source] Comparison of prostate and transition zone volume measured by the ellipsoid and planimetric methods with transrectal ultrasonography before seed implantation of prostate cancerINTERNATIONAL JOURNAL OF UROLOGY, Issue 2 2008Tetsuhiro Ikeda Abstract: A total of 122 men who were diagnosed with localized prostatic cancer underwent transrectal ultrasound and the volumes of their prostates and transitional zones were obtained using the planimetric method and the ellipsoid method. Mean age was 64.2 ±13.4 (48.2,85.8), and mean preimplant prostate specific antigen was 6.01 ± 2.35 mg/mL (0.92,15.5). The clinical stage was T1c in 70 patients, T2a in 46 and T2b in 6. Prostatic volumes and transitional zone volumes obtained by the planimetric method were 18 % and 39% greater than those obtained by the ellipsoid method, respectively. There were significant differences between the volumes obtained by the two different methods. However, there was a good correlation between the prostatic volume and the transitional zone volume obtained by both the ellipsoid method (r = 0.851) and the planimetric method (r = 0.908). The regression line of the prostate volume between these two methods was calculated as Value of power Doppler sonography with 3D reconstruction in preoperative diagnostics of extraprostatic tumor extension in clinically localized prostate cancerINTERNATIONAL JOURNAL OF UROLOGY, Issue 1 2008Miroslav Zalesky Aim: The aim of the study is to investigate the value of preoperative power Doppler sonography with 3D reconstruction (3D-PDS) for diagnostics of extraprostatic extension of prostate cancer. Patients and Methods: In the prospective study we examined 146 patients with clinically localized prostate cancer who underwent radical prostatectomy. Prior to surgery, each patient underwent 3D-PDS, transrectal ultrasound (TRUS), and digital rectal examination (DRE). Furthermore, we determined the prostate volume, prostate specific antigen (PSA) level, PSA density (PSAD), and Gleason score. The risk of locally advanced cancer was assessed using Partin tables. We determined the sensitivity, specificity, and predictive values of these diagnostic procedures. We plotted the receiver operating characteristic (ROC) curves and calculated the areas under the curves (AUC). Multivariate logistic regression was used to identify the significant predictors of extraprostatic tumor extension. Based on this we developed diagnostic nomograms maximizing the probability of accurate diagnosis. Results: The significant differences between patients with organ confined and locally advanced tumor (based on the postoperative assessment) were observed in the PSA levels (P < 0.014), PSAD (P < 0.004), DRE (P < 0.037), TRUS (P < 0.003), and 3D-PDS (P < 0.000). The highest AUC value of 0.776 (P < 0.000) was found for 3D-PDS. The observed AUC value for TRUS was 0.670 (P < 0.000) and for PSAD 0.639 (P < 0.004). In multivariate regression analysis, the PSAD, preoperative Gleason score, and 3D-PDS finding were identified as significant preoperative predictors of extraprostatic tumor extension. Conclusion: Our data suggest that the 3D-PDS is a valuable preoperative diagnostic examination to identify locally advanced prostate cancer. Therefore, it can be used to maximize the probability of the accurate diagnosis of extraprostatic tumor extension. [source] Lower urinary tract symptoms and risk of prostate cancer in Japanese menINTERNATIONAL JOURNAL OF UROLOGY, Issue 8 2006AKIO MATSUBARA Aim: Our aim was to investigate whether or not men with lower urinary tract symptoms are at increased risk of prostate cancer. Methods: A total of 3511 men aged 50,79 years who underwent mass screening for prostate cancer between 2002 and 2004 for the first time, and completed the International Prostate Symptom Score (IPSS) questionnaire at the time of the prostate specific antigen (PSA) test, were enrolled in the present study. All men with PSA values greater than 4.0 ng/mL were advised and encouraged to undergo transrectal systematic sextant biopsy. The number of cancers subsequently detected was compared between men with IPSS scores of 0,7 and 8,35. Results: Of the 3511 men, 219 (6.2%) had PSA values greater than 4 ng/mL, 178 (5.1%) underwent biopsy, and 51 (1.5%) were found to have prostate cancer. Although the PSA positivity rate for men with IPSS scores of 8,35 was significantly higher than that in the 0,7 group, there were no significant intergroup differences in the cancer detection rates for biopsied men and for total screened subjects. Multivariate logistic regression analysis revealed that prostate volume was the dominant predictor for the detection of prostate cancer, followed by PSA level, but the IPSS made no significant contribution. No significant difference was noted in the IPSS scores between men with cancer and the others of the same age group. Conclusions: Symptomatic Japanese men are not at higher risk of prostate cancer despite their higher PSA values compared with asymptomatic men of the same age group. [source] Value of prostate specific antigen ,1 -antichymotrypsin complex for the detection of prostate cancer in patients with a PSA level of 4.1,10.0ng/mL: Comparison with PSA-related parametersINTERNATIONAL JOURNAL OF UROLOGY, Issue 11 2001Hideaki Miyake Abstract Background: The aim of the present study was to evaluate the usefulness of prostate specific antigen ,1 -antichymotrypsin complex (PSA-ACT) in the differential diagnosis of prostate cancer in patients with a PSA level of 4.1,10.0 ng/mL compared to several PSA- and PSA-ACT-related parameters. Methods: Serum samples were obtained from 103 patients with no evidence of malignancy on biopsy and 29 with histologically confirmed prostate cancer. All patients had pretreatment serum PSA levels between 4.0 and 10.0 ng/mL. The different forms of serum PSA, including total PSA (tPSA), free PSA (fPSA) and PSA-ACT were measured using immunofluorometric techniques with different monoclonal antibodies against PSA and ACT. Furthermore, tPSA and PSA-ACT densities of the whole prostate (PSAD and ACTD, respectively) and the f-to-tPSA and the f-to-PSA-ACT ratios (F/T ratio and F/ACT ratio, respectively) were calculated. Results: The differences between patients with prostate cancer and benign prostatic disease were significant with respect to all six parameters examined in this study. Analysis of receiver operating characteristics revealed that the areas under the curve for PSA-ACT, ACTD and the F/ACT ratio were larger than those for tPSA, PSAD and the F/T ratio, respectively. However, there were no significant differences in discrimination between benign and malignant diseases among these six parameters. Conclusions: In patients who have an intermediate serum PSA level, PSA-ACT and its associated parameters may not be significantly superior in the differential diagnosis between prostate cancer and benign prostatic diseases compared to tPSA and its traditional relatives. [source] Testosterone Supplementation Therapy for Older Men: Potential Benefits and RisksJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 1 2003David A. Gruenewald MD Serum testosterone levels decline gradually and progressively with aging in men. Many manifestations associated with aging in men, including muscle atrophy and weakness, osteoporosis, reduced sexual functioning, and increased fat mass, are similar to changes associated with testosterone deficiency in young men. These similarities suggest that testosterone supplementation may prevent or reverse the effects of aging. A MEDLINE search was performed to identify studies of testosterone supplementation therapy in older men. A structured, qualitative review was performed of placebo-controlled trials that included men aged 60 and older and evaluated one or more physical, cognitive, affective, functional, or quality-of-life outcomes. Studies focusing on patients with severe systemic diseases and hormone deficiencies related to specific diseases were excluded. In healthy older men with low-normal to mildly decreased testosterone levels, testosterone supplementation increased lean body mass and decreased fat mass. Upper and lower body strength, functional performance, sexual functioning, and mood were improved or unchanged with testosterone replacement. Variable effects on cognitive function were reported, with improvements in some cognitive domains (e.g., spatial, working, and verbal memory). Testosterone supplementation improved exercise-induced coronary ischemia in men with coronary heart disease, whereas angina pectoris was improved or unchanged. In a few studies, men with low testosterone levels were more likely to experience improvements in lumbar bone mineral density, self-perceived functional status, libido, erectile function, and exercise-induced coronary ischemia with testosterone replacement than men with less marked testosterone deficiency. No major unfavorable effects on lipids were reported, but hematocrit and prostate specific antigen levels often increased. Based on these results, testosterone supplementation cannot be recommended at this time for older men with normal or low-normal testosterone levels and no clinical manifestations of hypogonadism. However, testosterone replacement may be warranted in older men with markedly decreased testosterone levels, regardless of symptoms, and in men with mildly decreased testosterone levels and symptoms or signs suggesting hypogonadism. The long-term safety and efficacy of testosterone supplementation remain uncertain. Establishment of evidence-based indications will depend on further demonstrations of favorable clinical outcomes and symptomatic, functional, and quality-of-life benefits in carefully performed, long-term, randomized, placebo-controlled clinical trials. J Am Geriatr Soc 51:101,115, 2003. [source] Biomarkers for prostate cancerJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 1 2009Eddy S. Leman Abstract The detection of prostate cancer using a blood test has by many standards changed the face of the disease. Despite this tremendous success, there are limitations attributed to the use of prostate specific antigen (PSA) as a means to screen and detect prostate cancer. PSA, as its name implies, is not specific for prostate cancer and as such is often found elevated in other prostatic diseases/symptoms associated with the aging male. Clearly, more specific marker(s) that could identify which individuals actually have prostate cancer and differentiate them from those without the disease would be of tremendous value. The search for more accurate and clinically useful biomarkers of prostate cancer has been extensive. This has focused on individual markers, as well as groups of markers. Included among these are PSA isoforms, pathological indicators and stains, nucleic acids and others. This article highlights the discovery of PSA as a first blood-based biomarker for prostate cancer detection, as well as other molecular biomarkers and their potential application in detection of the disease. J. Cell. Biochem. 108: 3,9, 2009. © 2009 Wiley-Liss, Inc. [source] Amino-terminus domain of the androgen receptor as a molecular target to prevent the hormonal progression of prostate cancerJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 1 2006Gang Wang Abstract Prostate cancer has a propensity to metastasize to the bone. Currently the only effective systemic treatment for these patients is androgen ablation therapy. However, the tumor will invariably progress to an androgen-independent stage and the patient will succumb to his disease within approximately 2 years. The earliest indication of hormonal progression is the rising titer of serum prostate specific antigen. Current evidence implicates the androgen receptor (AR) as a key factor in maintaining the growth of prostate cancer cells in an androgen-depleted state. Under normal conditions, binding of ligand activates the receptor, allowing it to effectively bind to its respective DNA element. However, AR is also transformed in the absence of androgen (ligand-independent activation) in prostate cells via multiple protein kinase pathways and the interleukin-6 (IL-6) pathway that converge upon the N-terminal domain of the AR. This domain is the main region for phosphorylation and is also critical for normal coregulator recruitment. Here we discuss evidence supporting the role of the AR, IL-6 and other protein kinase pathways in the hormonal progression of prostate cancer to androgen independence and the mechanisms involved in activation of the AR by these pathways. Receptor-targeted therapy, especially potential drugs targeting the N-terminal domain, may effectively prevent or delay the hormonal progression of AR-dependent prostate cancer. J. Cell. Biochem. 98: 36,53, 2006. © 2006 Wiley-Liss, Inc. [source] Detection of carcinomas in an asymptomatic Chinese population: advantage of screening with multiple tumor markersJOURNAL OF CLINICAL LABORATORY ANALYSIS, Issue 2 2006Kuo-Chien Tsao Abstract A total of 73,443 asymptomatic individuals were screened on a voluntary basis for cancer at Chang Gung Memorial Hospital in Taiwan using a panel of tumor markers, including alpha fetoprotein (AFP), CA 125, CA 15-3, CA 19-9, carcinoembryonic antigen (CEA), prostate specific antigen (PSA), chromogranin A (CgA), and squamous cell specific antigen (SCC). The results are derived from data collected from January 1998 to October 2003. A total of 210 cancers (approximately 0.3%) were detected, including cancers of the liver, lung, colon, prostate, stomach, pancreas, breast, cervix, ovary, and bladder. Of the tumor markers monitored, elevated CA 19-9, CEA, and CA 125 were the most frequently detected in a variety of cancers. It was surprising to find that many cancers were not detected by their dominant markers but by the elevation of tumor markers not recommended for monitoring their tumor activity. Screening with multiple circulating tumor markers provides improved sensitivity for cancer detection in asymptomatic individuals before they reach the fatal advanced stage. Screening with multiple tumor markers also allows cancers to be detected in the absence of their dominant markers. If we had not measured the multiple tumor markers, these cancers would have gone undetected. J. Clin. Lab. Anal. 20:42,46, 2006. © 2006 Wiley-Liss, Inc. [source] Diffusion-weighted MRI for monitoring tumor response to photodynamic therapyJOURNAL OF MAGNETIC RESONANCE IMAGING, Issue 2 2010Hesheng Wang MS Abstract Purpose: To examine diffusion-weighted MRI (DW-MRI) for assessing the early tumor response to photodynamic therapy (PDT). Materials and Methods: Subcutaneous tumor xenografts of human prostate cancer cells (CWR22) were initiated in athymic nude mice. A second-generation photosensitizer, Pc 4, was delivered to each animal by a tail vein injection 48 h before laser illumination. A dedicated high-field (9.4 Tesla) small animal MR scanner was used to acquire diffusion-weighted MR images pre-PDT and 24 h after the treatment. DW-MRI and apparent diffusion coefficients (ADC) were analyzed for 24 treated and 5 control mice with photosensitizer only or laser light only. Tumor size, prostate specific antigen (PSA) level, and tumor histology were obtained at different time points to examine the treatment effect. Results: Treated mice showed significant tumor size shrinkage and decrease of PSA level within 7 days after the treatment. The average ADC of the 24 treated tumors increased 24 h after PDT (P < 0.001) comparing with pre-PDT. The average ADC was 0.511 ± 0.119 × 10,3 mm2/s pre-PDT and 0.754 ± 0.181 × 10,3 mm2/s 24 h after the PDT. There is no significant difference in ADC values pre-PDT and 24 h after PDT in the control tumors (P = 0.20). Conclusion: The change of tumor ADC values measured by DW-MRI may provide a noninvasive imaging marker for monitoring tumor response to Pc 4-PDT as early as 24 h. J. Magn. Reson. Imaging 2010;32:409,417. © 2010 Wiley-Liss, Inc. [source] Heparin-binding proteins of human seminal plasma: purification and characterizationMOLECULAR REPRODUCTION & DEVELOPMENT, Issue 12 2008Vijay Kumar Abstract Human seminal plasma (HuSP) contains several proteins that bind heparin and related glycosaminoglycans. Heparin binding proteins (HBPs) from seminal plasma have been shown to participate in modulation of capacitation or acrosome reaction and thus have been correlated with fertility in some species. However, these have not been studied in detail in human. The objective of this study was to purify major HBPs from HuSP in order to characterize these proteins. HBPs were isolated by affinity,chromatography on Heparin,Sepharose column, purified by reverse-phase high-performance liquid chromatography (RP-HPLC) and Size-exclusion chromatography and checked for purity on sodium-dodecyl PAGE (SDS,PAGE). Identification of HBPs was done by matrix-assisted laser desorption-ionization-time-of-flight-mass spectrometry (MALDI-TOF-MS). Here we report the purification and identification of seven HBPs in seminal fluid. The major HBPs are lactoferrin and its fragments, semenogelin I fragments, semenogelin II, prostate specific antigen, homolog of bovine seminal plasma-proteins (BSP), zinc finger protein (Znf 169) and fibronectin fragments. In this study we are reporting for the first time the purification and identification of BSP-homolog and Znf 169 from HuSP and classified them as HBPs. Here we report the purification of seven clinically important proteins from human seminal fluid through heparin affinity chromatography and RP-HPLC, in limited steps with higher yield. Mol. Reprod. Dev. 75: 1767,1774, 2008. © 2008 Wiley-Liss, Inc. [source] Transrectal ultrasound-guided biopsy of prostate voxels identified as suspicious of malignancy on three-dimensional 1H MR spectroscopic imaging in patients with abnormal digital rectal examination or raised prostate specific antigen level of 4,10 ng/mlNMR IN BIOMEDICINE, Issue 1 2007Virendra Kumar Abstract Results of the evaluation of transrectal ultrasound (TRUS) guided needle biopsy of voxels identified as suspicious of malignancy on magnetic resonance spectroscopic imaging (MRSI) in a large cohort of men (n,=,83) with abnormal digital rectal examination (DRE) [prostate specific antigen (PSA) 0,4,ng/ml] or PSA less than 10,ng/ml, are reported. Three-dimensional 1H MRSI was carried out at 1.5 T using a pelvic-phased array coil in combination with an endorectal surface coil. Voxels were classified as suspicious of malignancy based on Cit/(Cho,+,Cr) metabolite ratio. TRUS-guided biopsy of suspicious voxels was performed using the z - and x -coordinates obtained from MR images and two to three cores were taken from the suspected site. A systematic sextant biopsy was also carried out. MRSI showed voxels suspicious of malignancy in 44 patients while biopsy revealed cancer in 11 patients (25%). Patients who were negative for malignancy on MRSI were also negative on biopsy. An overall sensitivity of 100%, specificity of 54%, negative predictive value of 100% and accuracy of 60% were obtained. The site of biopsy was confirmed (n,=,20) as a hypo-intense area on repeat MRI while repeat MRSI revealed high choline and low citrate. The overall success rate of MRI-directed TRUS-guided biopsy of 25% was higher compared with a 9% success rate achieved without MR guidance in another group of 120 patients. Our results indicate that TRUS-guided biopsy of suspicious area identified as malignant from MRSI can be performed using the coordinates of the voxel derived from MR images. This increases the detection rate of prostate cancer in men with PSA level <10,ng/ml or abnormal DRE and also demonstrates the potential of MR in routine clinical practice. Copyright © 2006 John Wiley & Sons, Ltd. [source] Regulation of PSA secretion and survival signaling by calcium-independent phopholipase A2, in prostate cancer cellsTHE PROSTATE, Issue 12 2009Thomas M. Nicotera Abstract BACKGROUND Serum prostate specific antigen (PSA) levels in prostate cancer patients serve as a useful biomarker for diagnosing and monitoring prostate cancer. Recently, secreted PSA has been characterized as an autocrine survival factor through activation of Akt and induction of AR. In the normal prostate, PSA is secreted in the lumen of prostatic ducts to lyse proteins in the seminal coagulum. METHODS However, the mechanism for constitutive PSA secretion from benign prostate and its transport across the prostate-blood barrier into serum are unknown. Regulation of peptide secretion by iPLA2 -, has been reported in non-prostatic tissue and in prostate tissue iPLA2 -, is reported to be under androgen regulation. We investigated whether iPLA2 plays a role for in PSA secretion by comparing iPLA2 activity and expression in normal prostate epithelial RWPE-1 cells and in LNCaP prostate cancer cells. Expression of the two active iPLA2 -, mRNA splice variants, LH-iPLA2 and SH-iPLA2, were increased and the inhibitory ankyrin-iPLA2 isoform was markedly reduced in LNCaP cells as compared to normal prostate epithelial RWPE-1 cells. RESULTS These changes are consistent with a higher enzymatic activity in LNCaP cells. The iPLA2 -,-specific inhibitor BEL inhibited PSA secretion and induced apoptosis in LNCaP cells. iPLA2 knockdown using SiRNA inhibited PSA secretion, downregulated AR and induced apoptosis. Exogenous PSA suppressed BEL-induced apoptosis and neutralizing anti-PSA antibody blocked the survival effect of PSA. CONCLUSIONS These data indicate that iPLA2 -, participates in regulating PSA secretion and supports the concept that secreted PSA provides an autocrine survival function in LNCaP cells. Prostate 69:1270,1280, 2009. © 2009 Wiley-Liss, Inc. [source] Quantitative RT-PCR analysis of estrogen receptor gene expression in laser microdissected prostate cancer tissueTHE PROSTATE, Issue 8 2009Thomas J. Walton Abstract BACKGROUND Real-time quantitative RT-PCR analysis of laser microdissected tissue is considered the most accurate technique for determining tissue gene expression. The discovery of estrogen receptor beta (ER,) has focussed renewed interest on the role of estrogen receptors in prostate cancer, yet few studies have utilized the technique to analyze estrogen receptor gene expression in prostate cancer. METHODS Fresh tissue was obtained from 11 radical prostatectomy specimens and from 6 patients with benign prostate hyperplasia. Pure populations of benign and malignant prostate epithelium were laser microdissected, followed by RNA isolation and electrophoresis. Quantitative RT-PCR was performed using primers for androgen receptor (AR), estrogen receptor beta (ER,), estrogen receptor alpha (ER,), progesterone receptor (PGR) and prostate specific antigen (PSA), with normalization to two housekeeping genes. Differences in gene expression were analyzed using the Mann,Whitney U -test. Correlation coefficients were analyzed using Spearman's test. RESULTS Significant positive correlations were seen when AR and AR-dependent PSA, and ER, and ER,-dependent PGR were compared, indicating a representative population of RNA transcripts. ER, gene expression was significantly over-expressed in the cancer group compared with benign controls (P,<,0.01). In contrast, PGR expression was significantly down-regulated in the cancer group (P,<,0.05). There were no significant differences in AR, ER, or PSA expression between the groups. This study represents the first to show an upregulation of ER, gene expression in laser microdissected prostate cancer specimens. CONCLUSIONS In concert with recent studies the findings suggest differential production of ER, splice variants, which may play important roles in the genesis of prostate cancer. Prostate 69: 810,819, 2009. © 2009 Wiley-Liss, Inc. [source] Androgen receptor or estrogen receptor-, blockade alters DHEA-, DHT-, and E2 -induced proliferation and PSA production in human prostate cancer cellsTHE PROSTATE, Issue 11 2007Julia T. Arnold Abstract BACKGROUND Dehydroepiandrosterone (DHEA) is an endogenous steroid that is metabolized to androgens and/or estrogens in the human prostate. DHEA levels decline with age, and use of DHEA supplements to retard the aging process is of unproved effectiveness and safety. LNCaP and LAPC-4 prostate cancer cells were used to determine whether DHEA-modulated proliferation and prostate specific antigen (PSA) production were mediated via the androgen receptor (AR) and/or ER,. METHODS Cells were treated with DHEA, DHT, or E2 and antagonists to AR (Casodex®-bicalutamide) or ER (ICI 182,780) or siRNA to the respective receptors. Proliferation was assessed by MTT assay and PSA mRNA and protein secretion were measured by quantitative real-time PCR and ELISA. Associations of AR and ER, were analyzed by co-immunoprecipitation studies and fluorescent confocal microscopy. RESULTS DHEA-, T-, and E2 -induced proliferation of LNCaP cells was blunted by Casodex but not by ICI treatment. In LNCaP cells, Casodex and ICI suppressed hormone-induced PSA production. In LAPC-4 cells, DHT-stimulated PSA mRNA was inhibited by Casodex and ICI, and the minimal stimulation by DHEA was inhibited by ICI. Use of siRNAs confirmed involvement of AR and ER, in hormone-induced PSA production while AR-ER, co-association was suggested by immunoprecipitation and nuclear co-localization. CONCLUSIONS These findings support involvement of both AR and ER, in mediating DHEA-, DHT-, and E2 -induced PSA expression in prostate cancer cells. Prostate 67: 1152,1162, 2007. © 2007 Wiley-Liss, Inc. [source] Regulation of prostate cancer cell growth and PSA expression by angiotensin II receptor blocker with peroxisome proliferator-activated receptor gamma ligand like actionTHE PROSTATE, Issue 9 2007Hitoshi Ishiguro Abstract BACKGROUND We previously reported that angiotensin II (AII) activated the proliferation of prostate cancer cells, and its antagonist, an AII receptor type 1 (AT1R) blocker (ARB), inhibited the proliferation of prostate cancer in vitro and in vivo. In the present study, we investigated whether telmisartan, an ARB, has a unique feature as a peroxisome proliferator-activated receptor , (PPAR,) ligand, and its suppressive potential on prostate cancer cells. METHODS Cell count or MTT assay were carried out for growth suppression of prostate cancer cells. Phosphorylation of mitogen-activated protein kinase (MAPK), specific expression of prostate specific antigen (PSA) and AT1R were investigated by western blot. To confirm the PPAR, activity of ARBs, luciferase assay using PSA promoter and PPAR, response elements (PPRE) plasmids was performed. RESULTS The results showed that cell proliferation and signal transduction were inhibited by telmisartan treatment. Also, inhibition of PSA expression by telmisartan was confirmed by western blot and luciferase assay, indicating that an ARB acted in a similar way such as an anti-androgenic agent in prostate cancer cells. CONCLUSION The present study showed ARBs, especially those possessing a PPAR, ligand-like structure, have a potential antagonistic effect on androgen-dependent and -independent prostate cancer. Prostate 67: 924,932, 2007. © 2007 Wiley-Liss, Inc. [source] Activation of innate immunity by prostate specific antigen (PSA),THE PROSTATE, Issue 15 2006James A. Kodak Abstract BACKGROUND Prostate specific antigen (PSA) is a serine protease secreted by the prostatic epithelium. The only known function of the protein is to cleave seminogelin. We wished to determine if PSA activated peripheral blood mononuclear cells (PBMC). METHODS PBMC and selected sub-populations were cultured with purified PSA. Secretion of IFN, was measured by cytokine capture flow cytometry and enzyme-linked immunosorbent assay. RESULTS We observed secretion of IFN, and a proliferative response in PBMC cultured with PSA. We found that NK cells were the source of the IFN, but NK cells were not directly stimulated by PSA. Rather, a soluble factor secreted primarily by CD14 monocytes in response to PSA stimulated NK cells to secrete IFN,. DISCUSSION PSA induces a pro-inflammatory response that results in the secretion of INF, by NK cells. The presence of large amounts of PSA could contribute to the common finding of inflammatory infiltrates in the prostate. Prostate 66: 1592,1599, 2006. Published 2006 Wiley-Liss, Inc. [source] Fast and novel purification method to obtain the prostate specific antigen (PSA) from human seminal plasmaTHE PROSTATE, Issue 10 2006Boris Acevedo Abstract Background Prostate specific antigen (PSA) is a relevant antigen in diagnosis; follow-up, and therapeutic approaches for fighting the prostate cancer. Several methods have been published previously to obtain a high purity preparation of PSA. In general, these methods are expensive, time-consuming, laborious, and in some cases produce low yields. Methods Based on a panel of 7 anti-PSA Mab's we carried on binding and elution experiments of PSA antigen in 96-well plates. The selected Mab were immobilized in a Sepharose CL-4B activated matrix with the purpose of purify PSA from human seminal fluid. In order to optimize the purification procedure, we test several washing and elution conditions (chaotropic agents, high ionic strength solution, and extreme pH). Results We selected a high ionic strength solution (2 M MgCl2) as elution condition, and a previous washing step with a mix of two ionic solutions (2.5 M NaCl pH 8/1 M MgCl2 pH 5.5) in order to purify PSA. Using such conditions we obtained a PSA preparation with 90% of purity and 50% of recovery. Conclusion In this article, we report a simple, quickly, and non-expensive procedure to obtain free-PSA from human seminal plasma at high purity levels. Prostate 66: 1029,1036, 2006. © 2006 Wiley-Liss, Inc. [source] T-cell recognition of a prostate specific antigen is not sufficient to induce prostate tissue destructionTHE PROSTATE, Issue 6 2006Jason R. Lees Abstract METHODS The ability of CD8+ T-cells to induce prostate inflammation was examined using a prostate ovalbumin expressing transgenic mouse (POET) and/or adoptive transfer of T-cell receptor (TCR) transgenic T-cells (OT-I) that specifically recognize ovalbumin. Localization of inflammatory cells to prostate tissue was examined following T-cell activation via endogenous prostatic antigen, recombinant type 5 adenovirus carrying the gene coding ovalbumin (Ad5-mOVA), or adoptive transfer of in vitro antigen stimulated OT-I cells. RESULTS Ovalbumin specific OT-I cells were activated by autologous prostate antigen and trafficked to the prostate, but did not induce inflammation unless present in overwhelming numbers (,65% of CD8+ T-cells). Activation of antigen specific CD8+ T-cells in vitro (peptide pulsed antigen presenting cells) or in vivo (Ad5-mOVA) induced transitory prostate inflammation, without induction of prostate pathology, regardless of CD4+ T-cell availability. Inflammation also was observed in OT-I,×,POET mice but again, pathological effects were not observed. CONCLUSIONS T lymphocytes specific for a prostate antigen are capable of inducing inflammatory infiltration of prostatic tissue rapidly following activation, but do not produce pathological prostate injury. Prostate 66:578,590, 2006. © 2005 Wiley-Liss, Inc. [source] In vivo real-time imaging of TGF-,-induced transcriptional activation of the RANK ligand gene promoter in intraosseous prostate cancerTHE PROSTATE, Issue 4 2004Jian Zhang Abstract BACKGROUND Current animal models of prostate cancer (CaP) bone metastasis do not allow measurement of either tumor growth in bone over time or activation of gene promoters in intraosseous tumors. To develop these methods, we used bioluminescent imaging (BLI) to determine if expression of receptor activator of NF-,B ligand (RANKL), a pro-osteoclastogenic factor that promotes CaP bone metastases, is modulated by the bone matrix protein transforming growth factor-, (TGF-,) in vivo. METHODS C4-2B human CaP cells were treated with TGF-, in vitro and RANKL mRNA and protein production were measured by polymerase chain reaction (PCR) and ELISA, respectively. Then C4-2B cells stably transfected with the RANKL promoter driving luciferase (lux) were injected intra-tibially into severe combined immundeficient (SCID) mice. Tumors were subjected to BLI every 2 weeks for 6 weeks and serum prostate specific antigen (PSA) was measured using ELISA. Vehicle (V), 1,25 dihydroxyvitamin D (VitD), or TGF-, was administered to mice with established tumors and BLI to measure RANKL promoter activity was performed. Tumors were then subjected to immunohistochemistry for lux and assayed for RANKL mRNA levels. RESULTS TGF-, induced RANKL protein and mRNA expression and activated the RANKL promoter activity in a dose-dependent manner in vitro. BLI demonstrated an increase in intraosseous tumor size over time, which correlated with serum PSA levels. Administration of TGF-, and VitD to mice with established intraosseous tumors increased lux activity compared to V. Intratibial tumor RANKL mRNA expression paralleled the increased promoter activity. Immunohistochemistry confirmed the presence of lux in the intraosseous tumors. CONCLUSIONS These results demonstrate the ability to measure intraosseous tumor growth over time and gene promoter activation in an established intraosseous tumor in vivo and also demonstrate that TGF-, induces activates the RANKL promoter. These results provide a novel method to explore the biology of CaP bone metastases. © 2004 Wiley-Liss, Inc. [source] Quantitative PSA RT-PCR for preoperative staging of prostate cancerTHE PROSTATE, Issue 4 2003Ralf Kurek Abstract BACKGROUND The clinical value of detecting prostate specific antigen (PSA) mRNA in the peripheral blood mononuclear cell fraction of patients (pts) by standard RT-PCR assays with localized prostate cancer remains controversial. We used a quantitative RT-PCR assay to measure the PSA mRNA copy number in addition to the qualitative PSA RT-PCR and correlated the results with clinical parameters. METHODS Total RNA was extracted from the peripheral blood mononuclear cell fraction of 115 prostate cancer pts prior to radical retropubic prostatectomy (RP) who received 3 months of neoadjuvant androgen deprivation. For quantitative RT-PCR, a PSA-like internal standard (IS) was added to each sample prior to reverse transcription and the PCR products for PSA and IS were selectively detected with fluorescent europium chelates after hybridization. Corresponding qualitative PSA,RT-PCR was performed for all samples. RESULTS The median PSA copy number was 126 (range: 0,37988). There were no significant correlations established between qualitative or quantitative RT-PCR results and given clinical parameters. Corresponding quantitative and qualitative RT-PCR results were significantly associated (P,=,0.01). CONCLUSIONS We were unable to show any additional value of quantitative as well as qualitative PSA RT-PCR for preoperative staging of prostate cancer so far. Nevertheless, the long-term follow up of the patients has to be awaited. Prostate 56: 263,269, 2003. © 2003 Wiley-Liss, Inc. [source] Response of patients with advanced prostatic cancer to administration of somatostatin analog RC-160 (vapreotide) at the time of relapseTHE PROSTATE, Issue 3 2003David González Barcena Abstract BACKGROUND The aim of this study was to evaluate the effects of administration of the somatostatin analog RC-160 (vapreotide) at the time of relapse in patients with androgen independent prostate cancer. METHODS Our study included 13 patients with biopsy-proven prostate cancer, stage D3. Eight patients had been treated with a depot formulation of the agonist D-Trp-6-LH-RH, with a median remission time of 68 (range 48,102 months). Five patients were initially treated by surgical orchiectomy, but relapsed after a median time of 33 months (range 17,91 months). A new remission period with a median duration of 10 months (range 2,29 months) was induced with Ketoconazole in the orchiectomy group. At the relapse time, all the patients received 1 mg of vapreotide t.i.d., by subcutaneous route, in addition to D-Trp-6-LH-RH, or Ketoconazole in the orchiectomy group. RESULTS Eight of 13 patients demonstrated clinical improvement after 3 months of therapy with vapreotide, six showing a decrease in serum prostate specific antigen (PSA) from 234.5,±,308.5 to 68.2,±,60.5 ng/ml (mean decline 71,±,8%; P,<,0.05). Two additional patients presented a fall in serum prostatic acid phosphatase (PAP). Responding patients showed a decrease in the bone pain score from 2.62,±,0.48 to 0.37,±,0.69 and an increase in the Karnofsky performance status from 72.3,±,4.21 to 83.6,±,23.2 (P,<,0.05). In accord with the ECOG criteria, two patients had a complete response; four had partial response, and two had a stable response. Four patients did not respond and one was not evaluable. Two patients died in remission, one at 16 months due to myocardial infarction and the other at 24 months due to pneumonia. Three patients relapsed at 5, 17, and 19 months respectively. Three patients who have been followed-up for more than 3 years continued in remission (79, 45, and 45 months) respectively. Vapreotide was well tolerated, only three patients having transitory mild diarrhea. CONCLUSIONS Our results indicate that therapy with the somatostatin analog vapreotide at the time of relapse can induce objective clinical responses in some patients with prostate cancer who are refractory to androgen ablation induced by LH-RH analogs or orchiectomy. Prostate 56: 183,191, 2003. © 2003 Wiley-Liss, Inc. [source] Possible mechanism of dexamethasone therapy for prostate cancer: Suppression of circulating level of interleukin-6THE PROSTATE, Issue 2 2003Koichiro Akakura Abstract BACKGROUND Glucocorticoids may have favorable effects on prostate cancer patients showing clinical and/or biochemical failure after androgen ablation. The efficacy and mechanisms of dexamethasone therapy as possible alternative endocrine therapy were investigated. METHODS Twenty five patients with prostate cancer treated by androgen ablation and showing a steady increase in serum prostate specific antigen (PSA) were treated with low-dose dexamethasone. RESULTS Of 25 patients, 11 demonstrated 50% or more decline of serum PSA and 9 showed improvement of pain on dexamethasone therapy. Of 8 patients who responded to dexamethasone thearpy, 5 had 80% or more decrease in serum interleukin-6 (IL-6). In contrast, none of 8 non-responders showed remarkable IL-6 suppression. Response of PSA was not correlated to the changes in serum dehydroepiandrosterone, dehydroepiandrosterone sulfate, or androstendione. CONCLUSIONS Significant suppression of serum IL-6, probably through inhibition of androgen-independent activation of androgen receptor, may be one of the mechanisms for the effect of dexamethasone therapy in prostate cancer patients with progressive disease. Prostate 56: 106,109, 2003. © 2003 Wiley-Liss, Inc. [source] Reduction of human prostate tumor vascularity by the ,1-adrenoceptor antagonist terazosinTHE PROSTATE, Issue 2 2001Kaspar Keledjian Abstract BACKGROUND We previously demonstrated that the quinazoline-derived a1-adrenoceptor antagonists doxazosin and terazosin suppress prostate cancer growth via apoptosis induction. The aim of this study was to determine the potential effect of a1-adrenoceptor antagonists on tumor vascularity of the human prostate. METHODS A total of 34 men with benign prostatic hyperplasia (BPH) who have been on terazosin treatment (for the obstructive symptoms) were pathologically diagnosed with prostate cancer following surgery. These patients were stratified according to the length of treatment periods with terazosin into two groups, 1 week,6 months, and 6,17 months. The control group consisted of prostatectomy specimens from 25 untreated prostate cancer patients undergoing surgery for localized disease. Formalin-fixed, paraffin-embedded prostate specimens were analyzed for apoptosis (TUNEL assay), cell proliferation (Ki-67), microvessel density (MVD) (von Willebrand factor/Factor VIII), vascular endothelial growth factor (VEGF) expression, and prostate specific antigen (PSA) immunoreactivity. RESULTS A significant induction of apoptosis was observed among cancerous prostatic epithelial cells in the terazosin-treated, as compared to the untreated prostate cancer specimens, while there was no significant change in the proliferative index of the same tumor cell populations after treatment. Furthermore, terazosin resulted in a significant decrease in prostate tissue MVD compared with the untreated group (P,<,0.01), that correlated with the increased apoptotic index of the cancerous areas. Tissue PSA expression in the prostatic tumor foci was also markedly reduced after terazosin treatment, while no significant changes in VEGF expression were detected. CONCLUSIONS These findings provide the first evidence that terazosin, a quinazoline-based a1-blocker decreases prostate tumor vascularity. Our study has significant clinical implications in identifying selected ,1-adrenoceptor antagonists as potential anti-tumor agents with apoptotic and anti-angiogenic effects in the human prostate that can be exploited for the treatment of advanced prostate cancer. Prostate 48:71,78, 2001. © 2001 Wiley-Liss, Inc. [source]
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